Substance addiction (e.g., drug addiction, alcohol addiction) is an illness. The path to addiction generally begins with the voluntary use of one or more controlled substances, such as narcotics, barbiturates, methamphetamines, alcohol, nicotine, and any of a variety of other such controlled substances. Over time, with extended use of the controlled substance(s), the voluntary ability to abstain from the controlled substance(s) is compromised due to the effects of prolonged use on brain function, and thus on behavior. As such, substance addiction generally is characterized by compulsive substance craving, seeking and use that persists even in the face of negative consequences. The cravings may represent changes in the underlying neurobiology of the patient which likely must be addressed in a meaningful way if recovery is to be obtained. Substance addiction is also characterized in many cases by withdrawal symptoms, which for some substances are life threatening (e.g., alcohol, barbiturates) and in others can result in substantial morbidity (which may include nausea, vomiting, fever, dizziness, and profuse sweating), distress, and decreased ability to obtain recovery.
For example, alcoholism, also known as alcohol dependence, is one such substance addiction. Alcoholism is primarily characterized by four symptoms, which include cravings, loss of control, physical dependence and tolerance. These symptoms also may characterize addictions to other controlled substances. The craving for alcohol, as well as other controlled substances, often is as strong as the need for food or water. Thus, an alcoholic may continue to drink despite serious family, health and/or legal ramifications.
Although alcoholism and other substance addictions generally cannot be cured, they can be treated. With treatment, many addicts are able to stop abusing a particular controlled substance and remain sober. However, treatment is not always effective. Many recovering addicts are unable to persistently resist cravings and other withdrawal symptoms indefinitely. Thus, some addicts have long periods of sobriety intermingled with bouts of relapse. Still others are unable to cease substance abuse for any appreciable length of time. Accordingly, a technique for reducing or eliminating the occurrence or severity of such cravings and withdrawal symptoms, thereby enabling the addict to abstain from substance abuse, is desirable.
Substance related disorders are thought to be due to vulnerabilities or imbalances within certain neural systems within the brain, possibly on multiple levels. For example, the neural systems underlying reward, reinforcement, compulsions (repetitive, driven behaviors), cravings, etc. may all be involved. Different substance related disorders may be more correlated with one system or brain structure over another at different stages, for instance:                the mesolimbic dopamine system is strongly associated with stimulants and cocaine        the locus coeruleus is strongly associated with opioid dependence        the basal ganglia is strongly associated compulsive behaviors        the orbitofrontal cortex is strongly associated with risk taking behavior        the amygdala is strongly associated with cue-induced relapse        the prefrontal cortex is strongly associated with stress-induced relapse.        
The “extended amygdala” is a concept that links many of the recent developments in understanding the neurobiology of drug reward, bridging work done among separate disorders. This is a brain area (bed nucleus of the stria terminalis, central medial amygdala, medial nucleus accumbens, and the sublenticular substantia inominata) that is strongly associated with determining the emotional salience of relevant stimuli and is probably a “final common pathway” for the neurobiology of substance related disorders.
Stimulation of the vagus affects many of the brain areas known to be involved in the neurobiology of substance related disorders, including fairly direct projections to the amygdala, locus coeruleus, orbitofrontal cortex, and basal ganglia. Furthermore, it indirectly affects the “extended amygdala” in ways that might restore the inherent imbalance of that system in individuals who suffer from a substance related disorder. This might allow such individuals to simultaneously lessen the compulsive and risky behaviors associated with substance related disorders as well as increase the positive motivational aspects of behavior necessary to break the addictive cycle.